APStracts 3:0220C, 1996.

Both m1 and m3 receptors regulate exocrine secretion by mucous acini. Culp, D. J., W. Luo, L. A. Richardson, G. E. Watson, L. R. Latchney. University of Rochester, Department of Dental Research and of Pharmacology and Physiology, 601 Elmwood Avenue, Rochester, New York 14642

APStracts 3:0220C, 1996.

We investigate the role of m1 and m3 receptors in regulating exocrine secretion from acini isolated from rat sublingual glands. In secretion experiments we derive KB values from Schild regression analysis for the antagonists pirenzepine (61.0 nM) and 4 -diphenylacetoxy-N-methylpiperidine (4-DAMP; 1.06 nM). The KB for 4 -DAMP is similar to its Ki value (1.81 nM) determined from radioligand competition experiments. In contrast, the KB for pirenzepine is between its high-affinity (17.6 nM) and low-affinity (404 nM) Ki values. In separate secretion experiments, we found the m1 receptor antagonist, m1-toxin, induces a rightward shift in the concentration -response curve to muscarinic agonist and inhibits maximal secretion by 40%. The inhibitory effect of m1-toxin appears specific for m1 receptor blockade as the toxin abolishes acinar high-affinity pirenzepine binding sites and does not inhibit secretion induced by non-muscarinic agents. Additional pharmacological studies indicate muscarinic receptors do not function through putative neural elements within isolated acini. Our combined results are consistent with both m1 and m3 receptors directly regulating mucous acinar exocrine secretion and indicate m3 receptors alone are insufficient to induce a maximal muscarinic response.

Received 1 February 1996; accepted in final form 28 June 1996.
APS Manuscript Number C62-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996